Displaying publications 1 - 20 of 33 in total

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  1. Fulltext Preserve a Voucher Specimen! The Critical Need for Integrating Natural History Collections in Infectious Disease Studies
    Thompson CW, Phelps KL, Allard MW, Cook JA, Dunnum JL, Ferguson AW, et al.
    mBio, 2021 Jan 12;12(1).
    PMID: 33436435 DOI: 10.1128/mBio.02698-20
    Despite being nearly 10 months into the COVID-19 (coronavirus disease 2019) pandemic, the definitive animal host for SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), the causal agent of COVID-19, remains unknown. Unfortunately, similar problems exist for other betacoronaviruses, and no vouchered specimens exist to corroborate host species identification for most of these pathogens. This most basic information is critical to the full understanding and mitigation of emerging zoonotic diseases. To overcome this hurdle, we recommend that host-pathogen researchers adopt vouchering practices and collaborate with natural history collections to permanently archive microbiological samples and host specimens. Vouchered specimens and associated samples provide both repeatability and extension to host-pathogen studies, and using them mobilizes a large workforce (i.e., biodiversity scientists) to assist in pandemic preparedness. We review several well-known examples that successfully integrate host-pathogen research with natural history collections (e.g., yellow fever, hantaviruses, helminths). However, vouchering remains an underutilized practice in such studies. Using an online survey, we assessed vouchering practices used by microbiologists (e.g., bacteriologists, parasitologists, virologists) in host-pathogen research. A much greater number of respondents permanently archive microbiological samples than archive host specimens, and less than half of respondents voucher host specimens from which microbiological samples were lethally collected. To foster collaborations between microbiologists and natural history collections, we provide recommendations for integrating vouchering techniques and archiving of microbiological samples into host-pathogen studies. This integrative approach exemplifies the premise underlying One Health initiatives, providing critical infrastructure for addressing related issues ranging from public health to global climate change and the biodiversity crisis.
  2. Current Status of Training and Certification for Congenital Heart Surgery Around the World: Proceedings of the Meetings of the Global Council on Education for Congenital Heart Surgery of the World Society for Pediatric and Congenital Heart Surgery
    Tchervenkov CI, Herbst C, Jacobs JP, Al-Halees Z, Edwin F, Dearani JA, et al.
    World J Pediatr Congenit Heart Surg, 2021 05;12(3):394-405.
    PMID: 33942697 DOI: 10.1177/21501351211003520
    The optimal training of the highly specialized congenital heart surgeon is a long and complex process, which is a significant challenge in most parts of the world. The World Society for Pediatric and Congenital Heart Surgery (WSPCHS) has established the Global Council on Education for Congenital Heart Surgery as a nonprofit organization with the goal of assessing current training and certification and ultimately establishing standardized criteria for the training, evaluation, and certification of congenital heart surgeons around the world. The Global Council and the WSPCHS have reviewed the present status of training and certification for congenital cardiac surgery around the world. There is currently lack of consensus and standardized criteria for training in congenital heart surgery, with significant disparity between continents and countries. This represents significant obstacles to international job mobility of competent congenital heart surgeons and to the efforts to improve the quality of care for patients with Congenital Heart Disease worldwide. The purpose of this article is to summarize and document the present state of training and certification in congenital heart surgery around the world.
  3. Fulltext Metabolic syndrome components and prevalence of cardiovascular disease among type 2 diabetic patients in Malaysia
    Tan MC, Wong TW, Ng OC, Joseph A, Hejar AR
    Southeast Asian J. Trop. Med. Public Health, 2014 Jan;45(1):226-35.
    PMID: 24964674
    Metabolic syndrome (MetS) is common among patients with type 2 diabetes mellitus (T2DM) and increases the risk of cardiovascular disease (CVD) and all-cause mortality. The objective of this study was to investigate the association between the components of MetS and the prevalence of CVD among patients with T2DM. We studied 313 patients aged > or = 30 years diagnosed with T2DM at two tertiary care hospitals. Patients were recruited by systematic random sampling. Clinical data was obtained using an interviewer-administered structured questionnaire and from a review of their medical records. MetS was diagnosed using NCEP ATP III, WHO, IDF and the new Harmonized definitions. Specific MetS components such as BMI, waist circumference, waist-to-hip ratio, hypertension, HDL-C and triglyceride levels were evaluated to determine if they had an association with CVD. Thirty-six point one percent of the subjects had CVD. The mean age of the subjects was 55.7 +/- 9.2 years and the mean duration of having diabetes was 10.1 +/- 8.1 years. The overall prevalences of MetS (> or = 3 of 5 components) (95% CI) were 96.1% (94.0-98.3), 95.8% (93.6-98.1), 84.8% (80.8-88.9) and 97.7% (96.1-99.4) using NCEP ATP III, WHO, IDF and Harmonized definitions, respectively. Patients with MetS had a higher prevalence of CVD using NCEP ATP III (98.2% vs 93.5%), WHO (98.2% vs 93.0%), IDF (87.6% vs 82.0%) and Harmonized criteria (98.2% vs 96.0%). The greater the number of MetS components, the greater the chance of having CVD using three definitions for diagnosing MetS: WHO, IDF and Harmonized (p < 0.05). MetS and the combination of the individual components of MetS were significantly associated with CVD among type 2 diabetic patients in Malaysia. Aggressive treatment of MetS components is required to reduce cardiovascular risk in T2DM.
  4. Fulltext Surgical treatment of children with raised intra ocular pressures associated with sturge weber syndrome at Hospital Kuala Lumpur, Malaysia
    Premadeva CS, Norazah AR, Sunder R, Jamalia R, Joseph A
    Med J Malaysia, 2014 Jun;69(3):142-3.
    PMID: 25326358 MyJurnal
    No abstract available.
  5. Asian minorities in Asian countries: intersecting disparities affecting minoritised groups
    Dee EC, Paguio JA, Yao JS, Lim J, Lasco G
    Lancet Oncol, 2021 09;22(9):e381.
    PMID: 34478665 DOI: 10.1016/S1470-2045(21)00350-8
  6. Fulltext Cancer disparities in Southeast Asia: intersectionality and a call to action
    Feliciano EJG, Ho FDV, Yee K, Paguio JA, Eala MAB, Robredo JPG, et al.
    Lancet Reg Health West Pac, 2023 Dec;41:100971.
    PMID: 38053740 DOI: 10.1016/j.lanwpc.2023.100971
  7. Fulltext Relationship between retinal blood flow and arterial oxygen
    Cheng RW, Yusof F, Tsui E, Jong M, Duffin J, Flanagan JG, et al.
    J Physiol, 2016 Feb 01;594(3):625-40.
    PMID: 26607393 DOI: 10.1113/JP271182
    KEY POINTS: Vascular reactivity, the response of the vessels to a vasoactive stimulus such as hypoxia and hyperoxia, can be used to assess the vascular range of adjustment in which the vessels are able to compensate for changes in PO2. Previous studies in the retina have not accurately quantified retinal vascular responses and precisely targeted multiple PaO2 stimuli at the same time as controlling the level of carbon dioxide, thus precluding them from modelling the relationship between retinal blood flow and oxygen. The present study modelled the relationship between retinal blood flow and PaO2, showing them to be a combined linear and hyperbolic function. This model demonstrates that the resting tonus of the vessels is at the mid-point and that they have great vascular range of adjustment, compensating for decreases in oxygen above a PETCO2 of 32-37 mmHg but being limited below this threshold. Retinal blood flow (RBF) increases in response to a reduction in oxygen (hypoxia) but decreases in response to increased oxygen (hyperoxia). However, the relationship between blood flow and the arterial partial pressure of oxygen has not been quantified and modelled in the retina, particularly in the vascular reserve and resting tonus of the vessels. The present study aimed to determine the limitations of the retinal vasculature by modelling the relationship between RBF and oxygen. Retinal vascular responses were measured in 13 subjects for eight different blood gas conditions, with the end-tidal partial pressure of oxygen (PETCO2) ranging from 40-500 mmHg. Retinal vascular response measurements were repeated twice; using the Canon laser blood flowmeter (Canon Inc., Tokyo, Japan) during the first visit and using Doppler spectral domain optical coherence tomography during the second visit. We determined that the relationship between RBF and PaO2 can be modelled as a combination of hyperbolic and linear functions. We concluded that RBF compensated for decreases in arterial oxygen content for all stages of hypoxia used in the present study but can no longer compensate below a PETCO2 of 32-37 mmHg. These vessels have a great vascular range of adjustment, increasing diameter (8.5% arteriolar and 21% total venous area) with hypoxia (40 mmHg P ETC O2; P < 0.001) and decreasing diameter (6.9% arteriolar and 23% total venous area) with hyperoxia (500 mmHg PETCO2; P < 0.001) to the same extent. This indicates that the resting tonus is near the mid-point of the adjustment ranges at resting PaO2 where sensitivity is maximum.
  8. Build international biorepository capacity
    Colella JP, Agwanda BR, Anwarali Khan FA, Bates J, Carrión Bonilla CA, de la Sancha NU, et al.
    Science, 2020 11 13;370(6518):773-774.
    PMID: 33184198 DOI: 10.1126/science.abe4813
  9. Fulltext Monoallelic variants resulting in substitutions of MAB21L1 Arg51 Cause Aniridia and microphthalmia
    Hall HN, Bengani H, Hufnagel RB, Damante G, Ansari M, Marsh JA, et al.
    PLoS One, 2022;17(11):e0268149.
    PMID: 36413568 DOI: 10.1371/journal.pone.0268149
    Classical aniridia is a congenital and progressive panocular disorder almost exclusively caused by heterozygous loss-of-function variants at the PAX6 locus. We report nine individuals from five families with severe aniridia and/or microphthalmia (with no detectable PAX6 mutation) with ultrarare monoallelic missense variants altering the Arg51 codon of MAB21L1. These mutations occurred de novo in 3/5 families, with the remaining families being compatible with autosomal dominant inheritance. Mice engineered to carry the p.Arg51Leu change showed a highly-penetrant optic disc anomaly in heterozygous animals with severe microphthalmia in homozygotes. Substitutions of the same codon (Arg51) in MAB21L2, a close homolog of MAB21L1, cause severe ocular and skeletal malformations in humans and mice. The predicted nucleotidyltransferase function of MAB21L1 could not be demonstrated using purified protein with a variety of nucleotide substrates and oligonucleotide activators. Induced expression of GFP-tagged wildtype and mutant MAB21L1 in human cells caused only modest transcriptional changes. Mass spectrometry of immunoprecipitated protein revealed that both mutant and wildtype MAB21L1 associate with transcription factors that are known regulators of PAX6 (MEIS1, MEIS2 and PBX1) and with poly(A) RNA binding proteins. Arg51 substitutions reduce the association of wild-type MAB21L1 with TBL1XR1, a component of the NCoR complex. We found limited evidence for mutation-specific interactions with MSI2/Musashi-2, an RNA-binding proteins with effects on many different developmental pathways. Given that biallelic loss-of-function variants in MAB21L1 result in a milder eye phenotype we suggest that Arg51-altering monoallelic variants most plausibly perturb eye development via a gain-of-function mechanism.
  10. Microvascular thrombosis in pediatric multiple organ failure: Is it a therapeutic target?
    Nguyen T, Hall M, Han Y, Fiedor M, Hasset A, Lopez-Plaza I, et al.
    Pediatr Crit Care Med, 2001 Jul;2(3):187-196.
    PMID: 12793940
    PURPOSE: To discuss the current rationale for the use of specific and nonspecific therapies for thrombotic microangiopathy in thrombocytopenia-associated pediatric multiple organ failure syndromes. Methods: Pertinent PubMed and MEDLINE citations and proceedings of recent critical care meeting presentations were reviewed. RESULTS: Critical care clinicians have reported using antithrombin III concentrate, protein C concentrate, activated protein C, prostacyclin and its analogues, heparin, tissue factor pathway inhibitor concentrate, plasma infusion, plasma exchange, whole blood exchange, pentoxifylline, tissue plasminogen activator, urokinase, and streptokinase with perceived therapeutic benefits in patients with thrombocytopenia-associated multiple organ failure, including those with thrombotic thrombocytopenic purpura/hemolytic uremic syndrome, disseminated intravascular coagulation syndrome, and secondary thrombotic microangiopathy syndrome without prolonged prothrombin time/activated partial thromboplastin time. CONCLUSION: Assuming that underlying disease is remediable, a consensus has developed that thrombotic microangiopathy is a therapeutic target in children with thrombocytopenia-associated multiple organ failure syndromes. Studies are warranted to delineate efficacious use of specific and nonspecific therapies to prevent and reverse thrombotic microangiopathy in these patients.
  11. Fulltext Arbuscular mycorrhizal trees influence the latitudinal beta-diversity gradient of tree communities in forests worldwide
    Zhong Y, Chu C, Myers JA, Gilbert GS, Lutz JA, Stillhard J, et al.
    Nat Commun, 2021 May 25;12(1):3137.
    PMID: 34035260 DOI: 10.1038/s41467-021-23236-3
    Arbuscular mycorrhizal (AM) and ectomycorrhizal (EcM) associations are critical for host-tree performance. However, how mycorrhizal associations correlate with the latitudinal tree beta-diversity remains untested. Using a global dataset of 45 forest plots representing 2,804,270 trees across 3840 species, we test how AM and EcM trees contribute to total beta-diversity and its components (turnover and nestedness) of all trees. We find AM rather than EcM trees predominantly contribute to decreasing total beta-diversity and turnover and increasing nestedness with increasing latitude, probably because wide distributions of EcM trees do not generate strong compositional differences among localities. Environmental variables, especially temperature and precipitation, are strongly correlated with beta-diversity patterns for both AM trees and all trees rather than EcM trees. Results support our hypotheses that latitudinal beta-diversity patterns and environmental effects on these patterns are highly dependent on mycorrhizal types. Our findings highlight the importance of AM-dominated forests for conserving global forest biodiversity.
  12. Complexity of avian evolution revealed by family-level genomes
    Stiller J, Feng S, Chowdhury AA, Rivas-González I, Duchêne DA, Fang Q, et al.
    Nature, 2024 Apr 01.
    PMID: 38560995 DOI: 10.1038/s41586-024-07323-1
    Despite tremendous efforts in the past decades, relationships among main avian lineages remain heavily debated without a clear resolution. Discrepancies have been attributed to diversity of species sampled, phylogenetic method and the choice of genomic regions1-3. Here we address these issues by analysing the genomes of 363 bird species4 (218 taxonomic families, 92% of total). Using intergenic regions and coalescent methods, we present a well-supported tree but also a marked degree of discordance. The tree confirms that Neoaves experienced rapid radiation at or near the Cretaceous-Palaeogene boundary. Sufficient loci rather than extensive taxon sampling were more effective in resolving difficult nodes. Remaining recalcitrant nodes involve species that are a challenge to model due to either extreme DNA composition, variable substitution rates, incomplete lineage sorting or complex evolutionary events such as ancient hybridization. Assessment of the effects of different genomic partitions showed high heterogeneity across the genome. We discovered sharp increases in effective population size, substitution rates and relative brain size following the Cretaceous-Palaeogene extinction event, supporting the hypothesis that emerging ecological opportunities catalysed the diversification of modern birds. The resulting phylogenetic estimate offers fresh insights into the rapid radiation of modern birds and provides a taxon-rich backbone tree for future comparative studies.
  13. Awe, curiosity, and multicultural experience
    Zhang JW, Howell RT, Januchowski JA, Ramis T, Mello Z, Monroy M
    J Pers, 2023 Jun;91(3):667-682.
    PMID: 35929345 DOI: 10.1111/jopy.12766
    INTRODUCTION: Despite broad consensus about multicultural experience's benefits, there is a lack of research on the antecedents to multicultural experiences. Research has indicated that awe shifts attention away from the self toward larger entities, which could include elements of other cultures.

    METHODS: Four studies (N = 2915) tested whether trait, daily, and induced awe promoted multicultural experience.

    RESULTS: Studies 1-2 (adolescents, young, middle, and older adults) showed that trait awe predicted greater multicultural identity and experience independent of other positive emotions and openness. Study 3 (students & adults in U.S. & Malaysia) demonstrated that daily awe predicted more daily multicultural experience independent of yesterday's multicultural experience. These results were explained by trait and daily curiosity. Study 4 (adults) found that induction of awe increased state multicultural identity and experience via state curious emotions and then state curious personality.

    CONCLUSION: We found that experiencing more awe can be a tool for enhancing the multicultural experience. The discussion focuses on the implications for future research on awe and multicultural experiences.

  14. Molecular docking and dynamics supported investigation of antiviral activity of Lichen metabolites of Roccella montagnei: an in silico and in vitro study
    Bhat NB, Das S, Sridevi BVS, H RC, Nayaka S, S N, et al.
    J Biomol Struct Dyn, 2023;41(21):11484-11497.
    PMID: 36803674 DOI: 10.1080/07391102.2023.2180666
    Lichens are symbiotic organisms that have been traditionally used for treating different kinds of ailments. As there are only a few reports on the antiviral activity of lichens, we thought of evaluating the anti-Herpes simplex virus-1 (HSV-1) activity of methanolic extract of Roccella montagnei and their isolated compounds. Fractionation of crude methanolic extract of Roccella montagnei by column chromatography isolated two pure compounds. Antiviral activity was assessed using a CPE inhibition assay at non-cytotoxic concentrations on Vero cells. Molecular docking and dynamics studies were carried out against Herpes simplex type-1 thymidine kinase to understand the binding interactions of the isolated compounds with reference to acyclovir. Isolated compounds were characterized as methyl orsellinate and montagnetol by spectral methods. Methanolic extract of Roccella montagnei exhibited an EC50 value of 56.51 µg/ml, while the compounds methyl orsellinate and montagnetol offered EC50 values of 13.50 µg/ml and 37.52 µg/ml, respectively, against HSV-1 viral infection on Vero cell lines. The selectively index (SI) of montagnetol (10.93) was found to be higher when compared to that of methyl orsellinate (5.55), indicating its better anti-HSV-1 activity. The docking and dynamics studies showed montagnetol was stable throughout the 100 ns, having better interactions and docking scores with HSV-1 thymidine kinase than methyl orsellinate, as well as the standard. To understand the mechanism of montagnetol's anti-HSV-1 activity, more research is required, and this could lead to the discovery of new and effective antiviral agents.Communicated by Ramaswamy H. Sarma.
  15. Fulltext Global and National Burden of Diseases and Injuries Among Children and Adolescents Between 1990 and 2013: Findings From the Global Burden of Disease 2013 Study
    Global Burden of Disease Pediatrics Collaboration, Kyu HH, Pinho C, Wagner JA, Brown JC, Bertozzi-Villa A, et al.
    JAMA Pediatr, 2016 Mar;170(3):267-87.
    PMID: 26810619 DOI: 10.1001/jamapediatrics.2015.4276
    IMPORTANCE: The literature focuses on mortality among children younger than 5 years. Comparable information on nonfatal health outcomes among these children and the fatal and nonfatal burden of diseases and injuries among older children and adolescents is scarce.

    OBJECTIVE: To determine levels and trends in the fatal and nonfatal burden of diseases and injuries among younger children (aged <5 years), older children (aged 5-9 years), and adolescents (aged 10-19 years) between 1990 and 2013 in 188 countries from the Global Burden of Disease (GBD) 2013 study.

    EVIDENCE REVIEW: Data from vital registration, verbal autopsy studies, maternal and child death surveillance, and other sources covering 14,244 site-years (ie, years of cause of death data by geography) from 1980 through 2013 were used to estimate cause-specific mortality. Data from 35,620 epidemiological sources were used to estimate the prevalence of the diseases and sequelae in the GBD 2013 study. Cause-specific mortality for most causes was estimated using the Cause of Death Ensemble Model strategy. For some infectious diseases (eg, HIV infection/AIDS, measles, hepatitis B) where the disease process is complex or the cause of death data were insufficient or unavailable, we used natural history models. For most nonfatal health outcomes, DisMod-MR 2.0, a Bayesian metaregression tool, was used to meta-analyze the epidemiological data to generate prevalence estimates.

    FINDINGS: Of the 7.7 (95% uncertainty interval [UI], 7.4-8.1) million deaths among children and adolescents globally in 2013, 6.28 million occurred among younger children, 0.48 million among older children, and 0.97 million among adolescents. In 2013, the leading causes of death were lower respiratory tract infections among younger children (905.059 deaths; 95% UI, 810,304-998,125), diarrheal diseases among older children (38,325 deaths; 95% UI, 30,365-47,678), and road injuries among adolescents (115,186 deaths; 95% UI, 105,185-124,870). Iron deficiency anemia was the leading cause of years lived with disability among children and adolescents, affecting 619 (95% UI, 618-621) million in 2013. Large between-country variations exist in mortality from leading causes among children and adolescents. Countries with rapid declines in all-cause mortality between 1990 and 2013 also experienced large declines in most leading causes of death, whereas countries with the slowest declines had stagnant or increasing trends in the leading causes of death. In 2013, Nigeria had a 12% global share of deaths from lower respiratory tract infections and a 38% global share of deaths from malaria. India had 33% of the world's deaths from neonatal encephalopathy. Half of the world's diarrheal deaths among children and adolescents occurred in just 5 countries: India, Democratic Republic of the Congo, Pakistan, Nigeria, and Ethiopia.

    CONCLUSIONS AND RELEVANCE: Understanding the levels and trends of the leading causes of death and disability among children and adolescents is critical to guide investment and inform policies. Monitoring these trends over time is also key to understanding where interventions are having an impact. Proven interventions exist to prevent or treat the leading causes of unnecessary death and disability among children and adolescents. The findings presented here show that these are underused and give guidance to policy makers in countries where more attention is needed.

  16. Fulltext Early life exposure to farm animals and symptoms of asthma, rhinoconjunctivitis and eczema: an ISAAC Phase Three Study
    Brunekreef B, Von Mutius E, Wong GK, Odhiambo JA, Clayton TO, ISAAC Phase Three Study Group
    Int J Epidemiol, 2012 Jun;41(3):753-61.
    PMID: 22287135 DOI: 10.1093/ije/dyr216
    Associations between early life exposure to farm animals and respiratory symptoms and allergy in children have been reported in developed countries, but little is known about such associations in developing countries.
  17. Fulltext Dietary flavonoid intake and colorectal cancer risk in the European prospective investigation into cancer and nutrition (EPIC) cohort
    Zamora-Ros R, Barupal DK, Rothwell JA, Jenab M, Fedirko V, Romieu I, et al.
    Int J Cancer, 2017 Apr 15;140(8):1836-1844.
    PMID: 28006847 DOI: 10.1002/ijc.30582
    Flavonoids have been shown to inhibit colon cancer cell proliferation in vitro and protect against colorectal carcinogenesis in animal models. However, epidemiological evidence on the potential role of flavonoid intake in colorectal cancer (CRC) development remains sparse and inconsistent. We evaluated the association between dietary intakes of total flavonoids and their subclasses and risk of development of CRC, within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. A cohort of 477,312 adult men and women were recruited in 10 European countries. At baseline, dietary intakes of total flavonoids and individual subclasses were estimated using centre-specific validated dietary questionnaires and composition data from the Phenol-Explorer database. During an average of 11 years of follow-up, 4,517 new cases of primary CRC were identified, of which 2,869 were colon (proximal = 1,298 and distal = 1,266) and 1,648 rectal tumours. No association was found between total flavonoid intake and the risk of overall CRC (HR for comparison of extreme quintiles 1.05, 95% CI 0.93-1.18; p-trend = 0.58) or any CRC subtype. No association was also observed with any intake of individual flavonoid subclasses. Similar results were observed for flavonoid intake expressed as glycosides or aglycone equivalents. Intake of total flavonoids and flavonoid subclasses, as estimated from dietary questionnaires, did not show any association with risk of CRC development.
  18. Fulltext Metabolic perturbations prior to hepatocellular carcinoma diagnosis: Findings from a prospective observational cohort study
    Stepien M, Keski-Rahkonen P, Kiss A, Robinot N, Duarte-Salles T, Murphy N, et al.
    Int J Cancer, 2021 Feb 01;148(3):609-625.
    PMID: 32734650 DOI: 10.1002/ijc.33236
    Hepatocellular carcinoma (HCC) development entails changes in liver metabolism. Current knowledge on metabolic perturbations in HCC is derived mostly from case-control designs, with sparse information from prospective cohorts. Our objective was to apply comprehensive metabolite profiling to detect metabolites whose serum concentrations are associated with HCC development, using biological samples from within the prospective European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (>520 000 participants), where we identified 129 HCC cases matched 1:1 to controls. We conducted high-resolution untargeted liquid chromatography-mass spectrometry-based metabolomics on serum samples collected at recruitment prior to cancer diagnosis. Multivariable conditional logistic regression was applied controlling for dietary habits, alcohol consumption, smoking, body size, hepatitis infection and liver dysfunction. Corrections for multiple comparisons were applied. Of 9206 molecular features detected, 220 discriminated HCC cases from controls. Detailed feature annotation revealed 92 metabolites associated with HCC risk, of which 14 were unambiguously identified using pure reference standards. Positive HCC-risk associations were observed for N1-acetylspermidine, isatin, p-hydroxyphenyllactic acid, tyrosine, sphingosine, l,l-cyclo(leucylprolyl), glycochenodeoxycholic acid, glycocholic acid and 7-methylguanine. Inverse risk associations were observed for retinol, dehydroepiandrosterone sulfate, glycerophosphocholine, γ-carboxyethyl hydroxychroman and creatine. Discernible differences for these metabolites were observed between cases and controls up to 10 years prior to diagnosis. Our observations highlight the diversity of metabolic perturbations involved in HCC development and replicate previous observations (metabolism of bile acids, amino acids and phospholipids) made in Asian and Scandinavian populations. These findings emphasize the role of metabolic pathways associated with steroid metabolism and immunity and specific dietary and environmental exposures in HCC development.
  19. Fulltext Fighting Cancer around the World: A Framework for Action
    Horgan D, Mia R, Erhabor T, Hamdi Y, Dandara C, Lal JA, et al.
    Healthcare (Basel), 2022 Oct 25;10(11).
    PMID: 36360466 DOI: 10.3390/healthcare10112125
    Tackling cancer is a major challenge right on the global level. Europe is only the tip of an iceberg of cancer around the world. Prosperous developed countries share the same problems besetting Europe-and the countries and regions with fewer resources and less propitious conditions are in many cases struggling often heroically against a growing tide of disease. This paper offers a view on these geographically wider, but essentially similar, challenges, and on the prospects for and barriers to better results in this ceaseless battle. A series of panels have been organized by the European Alliance for Personalised Medicine (EAPM) to identify different aspects of cancer care around the globe. There is significant diversity in key issues such as NGS, RWE, molecular diagnostics, and reimbursement in different regions. In all, it leads to disparities in access and diagnostics, patients' engagement, and efforts for a better understanding of cancer.
  20. Framework for Adoption of Next-Generation Sequencing (NGS) Globally in the Oncology Area
    Horgan D, Hamdi Y, Lal JA, Nyawira T, Meyer S, Kondji D, et al.
    Healthcare (Basel), 2023 Feb 02;11(3).
    PMID: 36767006 DOI: 10.3390/healthcare11030431
    Radical new possibilities of improved treatment of cancer are on offer from an advanced medical technology already demonstrating its significance: next-generation sequencing (NGS). This refined testing provides unprecedentedly precise diagnoses and permits the use of focused and highly personalized treatments. However, across regions globally, many cancer patients will continue to be denied the benefits of NGS as long as some of the yawning gaps in its implementation remain unattended. The challenges at the regional and national levels are linked because putting the solutions into effect is highly dependent on cooperation between regional- and national-level cooperation, which could be hindered by shortfalls in interpretation or understanding. The aim of the paper was to define and explore the necessary conditions for NGS and make recommendations for effective implementation based on extensive exchanges with policy makers and stakeholders. As a result, the European Alliance for Personalised Medicine (EAPM) developed a maturity framework structured around demand-side and supply-side issues to enable interested stakeholders in different countries to self-evaluate according to a common matrix. A questionnaire was designed to identify the current status of NGS implementation, and it was submitted to different experts in different institutions globally. This revealed significant variability in the different aspects of NGS uptake. Within different regions globally, to ensure those conditions are right, this can be improved by linking efforts made at the national level, where patients have needs and where care is delivered, and at the global level, where major policy initiatives in the health field are underway or in preparation, many of which offer direct or indirect pathways for building those conditions. In addition, in a period when consensus is still incomplete and catching up is needed at a political level to ensure rational allocation of resources-even within individual countries-to enable the best ways to make the necessary provisions for NGS, a key recommendation is to examine where closer links between national and regional actions could complement, support, and mutually reinforce efforts to improve the situation for patients.
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